The Type of Sialic Acid

The majority of sialic acids have been detected in glycosidically linked form, but there are tissues and secretions containing relatively constant, although rather variable levels of free sialic acids. Free sialic acids are generally present in low concentrations in tissues. Significant amounts of free sialic acid were found in trout eggs (Warren 1960), and this varied with the stage of development of these fishes (Rahmann and Breer 1976). The seminal vesicle secretion of the Chinese hamster contains small amounts of free sialic acid (Fouquet 1971), and the 

Increased levels of sialic acid in human urine have been reported in Salla disease, 165-350 (xmole Neu5Ac being excreted per day, thus corresponding to a 10-fold increase over normal levels (Renlund et al. 1979). 

Glycosidically Linked Sialic Acids a) The Type of Sialic Acid 

The current knowledge on sialic acid derivatives in nature is presented in Table 1. Two parent molecules, differing in their N-acylation, Neu5Ac and Neu5Gc, are found. In addition, substitution of the hydroxyl groups at C-4, C-7, C-8 and C-9 by acetyl, glycolyl, lactyl, methyl, sulphate and phosphate moieties occurs and the number of possible derivatives becomes very large. This is important because of its potential for informational representation, as is discussed in section XI. 3. b). Evolutionary aspects are discussed in section XII. 

The linkage of single sialyl units to oligosaccharide chains (see Table 2) involves -glycosidic bonds between the C-2 anomeric hydroxyl group of sialic acid and the C-3, C-4 or C-6 hydroxyl groups of the penultimate non-sialic acid 

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Thus, the sialoglycolipids from E. retifera and A. amurensis starfish, which are closely related, contain an amino sugar, absent from the sialoglycolipids of other species of echinoderm, and possess the same trisaccharide chain-structure for the asialo derivative. They differ, however, in the type of sialic acids, and their location in the carbohydrate chain. 

Sialic acids are a family of nine-carbon acidic monosaccharides based on 3-deoxy nonulosonic acid (Fig. 17.4, also see Chapter 5). In 1952, the biochemist Gunnar Blix introduced the term sialic acid from the Greek aaXia (salia) or saliva after isolating this molecule from the salivary gland mucin. Sialic acid is now the generic term for the family that includes derivatives with a C5-amino substituent called neuraminic acid. Neu5Ac (5) is the type of sialic acid found in humans [47],... 

In addition to using MOE to improve the presentation of the normal sugars on glycoproteins, such as the human Neu5Ac form of sialic acid derived from ManNAc feeding, this methodology can be extended to control the type of sialic acid added to recombinant therapeutics. For example, Viswanathan and co-workers showed that mannose-6-phosphate, used in place of ManNAc, allowed their glycoengineered insect cells to produce the 2-keto-... 

The sialidases provide another example of a group of enzymes which show specificity for the type of complex carbohydrate, the nature of the glycosidic linkage (see section IV. 3. h) and the type of sialic acid (sections IV. 3.e) and f). 

N-Acetylneur-aminic acid Sialic acid (nine C atoms) NeuAc CMP-NeuAc Often the terminal sugar in both N- and 0-linked glycoproteins. Other types of sialic acid are also found, but NeuAc is the major species found in humans. Acetyl groups may also occur as 0-acetyl species as well as N-acetyl. 

Although the different methods for the analysis of sialic acids thus far described give some insight into the structure of these compounds, mass spectrometry permits unambiguous determination of the chain length and the number, type, and position of N- or O-acyl substituents in Neu derivatives. Thus, a variety of new and rare sialic acids have been discovered in the past few years, and the presence of known, mainly O-acetylated, sialic ac ids has been established in a variety of biological materials.34-37,62 85,94,95-97-96-10 -107-147-149... 

In all known types of CDG-I it has been observed that due to the loss of sialic acid residues, in addition to tetrasialo-transferrin, more or less pronounced di- and asialo-transferrin bands appear, which are evoked by the loss of either one or both complete oligosaccharide chains (Fig. 4.5.3, lanes 2-4). In contrast to CDG-I, changes in the charge of serum transferrin of most known CDG-II types are due to shortening of the oligosaccharide moieties (Fig. 4.5.3, lanes 5-7). 

Fig. 4.5.10 Analysis of core-1 mucin type -linked glycans derived from apolipoprotein C-III (ApoC-III). Serum-derived ApoC-III from a control (lane 1, left) and a CDG-IIx patient (lane 2, right) was investigated by IEF followed by antibody staining with a polyclonal rabbit-a-human ApoC-III antibody. ApoC-IIfi ApoC-IIEand ApoC-III0 indicate the variability in the amount of sialic acid residues linked to ApoC-III...

Mass spectrometry has been used successfully to establish the structure of sialic acids, and the type of their bonds in the oligosaccharide chain. For this purpose, the fragmentation of various derivatives containing both the cyclic and the acyclic forms of sialic acid has been comprehensively studied. The methyl esters of sialic acid methyl ketosides, obtained as a... 

TV-acetylneuraminic acid (the most common type of sialic acid = Sia), Sialic acid is a more general term including N- and O-substituted derivatives of neuraminic acid. Compounds in capital boldface type are the unmodified sugars or their amine derivatives. 

In vivo, pyruvate lyases perform a catabolic function. The synthetically most interesting types are those involved in the degradation of sialic acids or the structurally related octulosonic acid KDO, which are higher sugars typically found in mammalian or bacterial glycoconjugates [62-64], respectively. Also, hexose or pentose catabolism may proceed via pyruvate cleavage from intermediate 2-keto-3-deoxy derivatives which result from dehydration of the corresponding aldonic acids. Since these aldol additions are freely reversible, the often unfavourable equilibrium constants require that reactions in the direction of synthesis have to be driven by an excess of one of the components, preferably pyruvate for economic reasons, in order to achieve a satisfactory conversion. 

Our inhibition data, also taking into consideration the previous results [27a], show that the modifications on the structure of sialic acid increase the binding with HA, but not in an enough significant amount to use these type of analogues as anti-influenza drugs. 

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